BioPAX pathway converted from "Expression of ACSL1" in the Reactome database.LEFT-TO-RIGHTExpression of ACSL1The ACSL1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.Authored: May, B, 2011-11-08Reviewed: Kersten, S, 2009-06-08Edited: May, B, 2011-11-08ACSL1 geneReactome DB_ID: 5649949nucleoplasmGENE ONTOLOGYGO:0005654ENSEMBL:ENSG00000151726 ACSL1ACSL1FACL1FACL2LACSLACS1LACS2Homo sapiensNCBI Taxonomy9606ENSEMBLENSG00000151726Reactome Database ID Release 725649949Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5649949ReactomeR-HSA-56499491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5649949.1Reactomehttp://www.reactome.orgACSL1ACSL1 variant1Reactome DB_ID: 400123mitochondrial outer membraneGENE ONTOLOGYGO:0005741UniProt:P33121 ACSL1ACSL1FACL1FACL2LACSLACS1LACS2FUNCTION Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:24269233, PubMed:22633490). Preferentially uses palmitoleate, oleate and linoleate (PubMed:24269233). Preferentially activates arachidonate than epoxyeicosatrienoic acids (EETs) or hydroxyeicosatrienoic acids (HETEs) (By similarity).ACTIVITY REGULATION Inhibited at high temperature and by arachidonate.TISSUE SPECIFICITY Highly expressed in liver, heart, skeletal muscle, kidney and erythroid cells, and to a lesser extent in brain, lung, placenta and pancreas.DEVELOPMENTAL STAGE Expressed during the early stages of erythroid development while expression is very low in reticulocytes and young erythrocytes.SIMILARITY Belongs to the ATP-dependent AMP-binding enzyme family.UniProtP331211EQUAL698EQUALReactome Database ID Release 72400123Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400123ReactomeR-HSA-4001231Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-400123.1Reactome Database ID Release 721989778Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1989778ReactomeR-HSA-19897784Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1989778.419710929Pubmed2009Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and humanRakhshandehroo, MHooiveld, GMuller, MKersten, SanderPLoS One 4:e6796ACTIVATIONReactome Database ID Release 721989787Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1989787ReactomeR-HSA-19897871Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1989787.19353271Pubmed1997Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activatorsMartin, GSchoonjans, KLefebvre, AMStaels, BAuwerx, JJ Biol Chem 272:28210-7PPARA:RXRA Coactivator complexReactome DB_ID: 400154Converted from EntitySet in ReactomeCoactivators of PPARalphaReactome DB_ID: 400216KAT3ACREBBPCREB-binding proteinCBP_HUMANReactome DB_ID: 193545UniProt:Q92793 CREBBPCREBBPCBPFUNCTION Acetylates histones, giving a specific tag for transcriptional activation (PubMed:24616510). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10490106, PubMed:11154691, PubMed:12738767, PubMed:12929931, PubMed:9707565, PubMed:24207024, PubMed:28790157, PubMed:30540930). Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers (PubMed:14645221). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024). Acetylates DDX21, thereby inhibiting DDX21 helicase activity (PubMed:28790157). Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me) (PubMed:30540930). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493).SUBUNIT Found in a complex containing NCOA2; NCOA3; IKKA; IKKB and IKBKG. Probably part of a complex with HIF1A and EP300. Interacts with GATA1; the interaction results in acetylation and enhancement of transcriptional activity of GATA1. Interacts with MAF AND ZCCHC12. Interacts with DAXX; the interaction is dependent on CBP sumoylation and results in suppression of the transcriptional activity via recruitment of HDAC2 to DAXX (By similarity). Interacts with phosphorylated CREB1. Interacts with CITED4 (C-terminal region). Interacts (via the TAZ-type 1 domain) with HIF1A. Interacts with SRCAP, CARM1, ELF3, MLLT7/FOXO4, N4BP2, NCOA1, NCOA3, NCOA6, PCAF, DDX5, DDX17, PELP1, PML, SMAD1, SMAD2, SMAD3, SPIB and TRERF1. Interacts with KLF1; the interaction results in acetylation of KLF1 and enhancement of its transcriptional activity. Interacts with MTDH. Interacts with NFATC4. Interacts with MAFG; the interaction acetylates MAFG in the basic region and stimulates NFE2 transcriptional activity through increasing its DNA-binding activity. Interacts with IRF2; the interaction acetylates IRF2 and regulates its activity on the H4 promoter. Interacts with IRF3 (when phosphorylated); forming the dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I interferon genes (PubMed:27302953). Interacts (via N-terminus) with SS18L1/CREST (via C-terminus). Interacts with MECOM. Interacts with CITED1 (via C-terminus). Interacts with FOXO1; the interaction acetylates FOXO1 and inhibits its transcriptional activity. Interacts with NPAS2, CLOCK and ARNTL/BMAL1. Interacts with ASF1A and ASF1B; this promotes histone acetylation. Interacts with acetylated TP53/p53 and with the acetylated histones H3 and H4. Interacts (via transactivation domain and C-terminus) with PCNA; the interaction occurs on chromatin in UV-irradiated damaged cells (PubMed:24939902). Interacts with DHX9 (via N-terminus); this interaction mediates association with RNA polymerase II holoenzyme and stimulates CREB-dependent transcriptional activation (PubMed:9323138). Interacts with SMAD4; negatively regulated by ZBTB7A (PubMed:25514493). Interacts with DUX4 (via C-terminus) (PubMed:26951377). Forms a complex with KMT2A and CREB1 (PubMed:23651431).SUBUNIT (Microbial infection) Interacts with HTLV-1 Tax, p30II and HBZ.SUBUNIT (Microbial infection) Interacts with human herpes virus 8/HHV-8 protein vIRF-1; this interaction inhibits CREBBP binding to IRF3.SUBUNIT (Microbial infection) Interacts with HIV-1 Tat.DOMAIN The KIX domain mediates binding to HIV-1 Tat.PTM Methylation of the KIX domain by CARM1 blocks association with CREB. This results in the blockade of CREB signaling, and in activation of apoptotic response (By similarity).PTM Phosphorylated by CHUK/IKKA at Ser-1382 and Ser-1386; these phosphorylations promote cell growth by switching the binding preference of CREBBP from TP53 to NF-kappa-B.PTM Sumoylation negatively regulates transcriptional activity via the recruitment of DAAX.PTM Autoacetylation is required for binding to protein substrates, such as acetylated histones and acetylated TP53/p53.DISEASE Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with KMT2A/MLL1; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription.UniProtQ927931EQUAL2442EQUALReactome Database ID Release 72193545Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=193545ReactomeR-HSA-1935451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-193545.1CARM1Histone-arginine methyltransferase CARM1CARM1_HUMANPRMT4Reactome DB_ID: 400139UniProt:Q86X55 CARM1CARM1PRMT4FUNCTION Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B. Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue. Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs.ACTIVITY REGULATION Methylation of H3R17 (H3R17me) by CARM1 is stimulated by preacetylation of H3 'Lys-18' (H3K18ac) H3 'Lys-23' (H3K23ac) by EP300 and blocked by citrullination of H3 'Arg-17' (H3R17ci) by PADI4.SUBUNIT Homodimer (Probable). Interacts with the C-terminus of NCOA2/GRIP1, NCO3/ACTR and NCOA1/SRC1. Part of a complex consisting of CARM1, EP300/P300 and NCOA2/GRIP1. Interacts with FLII, TP53, myogenic factor MEF2, EP300/P300, TRIM24, CREBBP and CTNNB1. Identified in a complex containing CARM1, TRIM24 and NCOA2/GRIP1. Interacts with NCOA3/SRC3. Interacts with SNRPC (By similarity). Interacts with NR1H4. Interacts with RELA.SUBUNIT (Microbial infection) Interacts with HTLV-1 protein Tax.TISSUE SPECIFICITY Overexpressed in prostate adenocarcinomas and high-grade prostatic intraepithelial neoplasia.PTM Auto-methylated on Arg-550. Methylation enhances transcription coactivator activity. Methylation is required for its role in the regulation of pre-mRNA alternative splicing (By similarity).PTM Phosphorylation at Ser-216 interferes with S-adenosyl-L-methionine binding and strongly reduces methyltransferase activity (By similarity). Phosphorylation at Ser-216 is strongly increased during mitosis, and decreases rapidly to a very low, basal level after entry into the G1 phase of the cell cycle. Phosphorylation at Ser-216 may promote location in the cytosol.SIMILARITY Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.UniProtQ86X551EQUAL608EQUALReactome Database ID Release 72400139Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400139ReactomeR-HSA-4001391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-400139.1MED1Reactome DB_ID: 212445UniProt:Q15648 MED1MED1ARC205CRSP1CRSP200DRIP205DRIP230PBPPPARBPPPARGBPRB18ATRAP220TRIP2FUNCTION Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (PubMed:10406464, PubMed:11867769, PubMed:12037571, PubMed:12218053, PubMed:12556447, PubMed:14636573, PubMed:15340084, PubMed:15471764, PubMed:15989967, PubMed:16574658, PubMed:9653119). Acts as a coactivator for GATA1-mediated transcriptional activation during erythroid differentiation of K562 erythroleukemia cells (PubMed:24245781).SUBUNIT Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. This subunit specifically interacts with a number of nuclear receptors in a ligand-dependent fashion including AR, ESR1, ESR2, PPARA, PPARG, RORA, RXRA, RXRG, THRA, THRB and VDR. Interacts with CTNNB1, GABPA, GLI3, PPARGC1A and TP53. Interacts with YWHAH. Interacts with CLOCK; this interaction requires the presence of THRAP3 (By similarity). Interacts with GATA1 and CCAR1. Interacts with NR4A3 (By similarity). Interacts (via IBM motif) with PSIP1 (via IBD domain); phosphorylation increases its affinity for PSIP1 (PubMed:29997176).TISSUE SPECIFICITY Ubiquitously expressed.PTM Phosphorylated by MAPK1 or MAPK3 during G2/M phase which may enhance protein stability and promote entry into the nucleolus (PubMed:16314496). Phosphorylation increases its interaction with PSIP1 (PubMed:29997176).SIMILARITY Belongs to the Mediator complex subunit 1 family.UniProtQ156481EQUAL1581EQUALReactome Database ID Release 72212445Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=212445ReactomeR-HSA-2124451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-212445.1NCOA1Nuclear receptor coactivator 1NCOA1_HUMANReactome DB_ID: 442496UniProt:Q15788 NCOA1NCOA1BHLHE74SRC1FUNCTION Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.SUBUNIT Interacts with the methyltransferase CARM1 (By similarity). Interacts with NCOA6 and NCOA2. Interacts with the FDL motif of STAT5A and STAT5B. Interacts with the LXXLL motif of STAT6. Interacts with STAT3 following IL-6 stimulation. Interacts with the basal transcription factor GTF2B. Interacts with the histone acetyltransferases EP300 and CREBBP. Interacts with PCAF, COPS5, NR3C1 and TTLL5/STAMP. Interacts with PSMB9. Interacts with UBE2L3; they functionally interact to regulate progesterone receptor transcriptional activity. Interacts with PRMT2 and DDX5. Interacts with ASXL1. Interacts with PRMT6. Interacts (via LXXLL 1, 2 and 3 motifs) with RORC (via AF-2 motif). Interacts in a ligand-dependent fashion with RXRA. Interacts with TRIP4. Interacts with NR4A3 (By similarity). Interacts with VDR.TISSUE SPECIFICITY Widely expressed.DOMAIN The C-terminal (1107-1441) part mediates the histone acetyltransferase (HAT) activity.DOMAIN Contains 7 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. LXXLL motifs 3, 4 and 5 are essential for the association with nuclear receptors. LXXLL motif 7, which is not present in isoform 2, increases the affinity for steroid receptors in vitro.PTM Sumoylated; sumoylation increases its interaction with PGR and prolongs its retention in the nucleus. It does not prevent its ubiquitination and does not exert a clear effect on the stability of the protein.PTM Ubiquitinated; leading to proteasome-mediated degradation. Ubiquitination and sumoylation take place at different sites.DISEASE A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.SIMILARITY Belongs to the SRC/p160 nuclear receptor coactivator family.UniProtQ157881EQUAL1441EQUALReactome Database ID Release 72442496Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=442496ReactomeR-HSA-4424961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-442496.1NCOA2NCOA2_HUMANReactome DB_ID: 376398UniProt:Q15596 NCOA2NCOA2BHLHE75SRC2TIF2FUNCTION Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues. Critical regulator of glucose metabolism regulation, acts as RORA coactivator to specifically modulate G6PC expression. Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3. Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-ARNTL/BMAL1 heterodimer (By similarity).SUBUNIT Present in a complex containing NCOA3, IKKA, IKKB, IKBKG and CREBBP. Interacts (via C-terminus) with CREBBP. Interacts with ESR1, HIF1A, NCOA1, APEX, NR3C1, NR3C2, CARM1, RARA, and RXRA. Present in a complex containing CARM1 and EP300/P300. Interacts with CASP8AP2 and TTLL5/STAMP. Interacts with PSMB9 and DDX5. Interacts (via LXXLL 1, 2 and 3 motifs) with RORA and RORC (via AF-2 motif). Interacts with RWDD3. Interacts with CLOCK and ARNTL/BMAL1 (By similarity). Interacts with NR4A3; potentiates the activity of the NR4A3 (By similarity). Interacts with NR1H3 (PubMed:19481530).DOMAIN Contains four Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors and are, at least in part, functionally redundant.DOMAIN The LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding.DOMAIN Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently.DISEASE Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.SIMILARITY Belongs to the SRC/p160 nuclear receptor coactivator family.UniProtQ155961EQUAL1464EQUALReactome Database ID Release 72376398Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=376398ReactomeR-HSA-3763981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-376398.1NCOA6NCOA6_HUMANReactome DB_ID: 376414UniProt:Q14686 NCOA6NCOA6AIB3KIAA0181RAP250TRBPFUNCTION Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Coactivates expression in an agonist- and AF2-dependent manner. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ERs), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Probably functions as a general coactivator, rather than just a nuclear receptor coactivator. May also be involved in the coactivation of the NF-kappa-B pathway. May coactivate expression via a remodeling of chromatin and its interaction with histone acetyltransferase proteins.SUBUNIT Monomer and homodimer. Interacts with RBM39 (By similarity). Interacts in vitro with the basal transcription factors GTF2A and TBP, suggesting an autonomous transactivation function. Interacts with NCOA1, CRSP3, RBM14, the histone acetyltransferases EP300 and CREBBP, and with the methyltransferases NCOA6IP and PRMT2/HRMT1L1. Component of the MLL2/3 complex (also named ASCOM complex), at least composed of KMT2D/MLL2 or KMT2C/MLL3, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A, PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin. Interacts with ZNF335; may enhance ligand-dependent transcriptional activation by nuclear hormone receptors.TISSUE SPECIFICITY Ubiquitous. Highly expressed in brain, prostate, testis and ovary; weakly expressed in lung, thymus and small intestine.DOMAIN Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. Only motif 1 is essential for the association with nuclear receptors, while adjacent Ser-884 displays selectivity for nuclear receptors.PTM Phosphorylated by PRKDC.PTM Phosphorylation on Ser-884 leads to a strong decrease in binding to ESR1 and ESR2.MISCELLANEOUS Frequently amplified or overexpressed in colon, breast and lung cancers.UniProtQ146861EQUAL2063EQUALReactome Database ID Release 72376414Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=376414ReactomeR-HSA-3764141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-376414.1HELZ2PRIC285Peroxisomal proliferator-activated receptor A-interacting complex 285 kDa proteinPR285_HUMANReactome DB_ID: 442499UniProt:Q9BYK8 HELZ2HELZ2KIAA1769PRIC285FUNCTION Helicase that acts as a transcriptional coactivator for a number of nuclear receptors including PPARA, PPARG, THRA, THRB and RXRA.SUBUNIT Interacts with PPARA (via DNA-binding domain) and PPARG; the interaction stimulates the transcriptional activity of PPARA and PPARG. Interacts with THRAP3; the interaction is direct and HELZ2 and THRAP3 synergistically enhance the transcriptional activity of PPARG. It is probably part of the peroxisome proliferator activated receptor alpha interacting complex (PRIC).TISSUE SPECIFICITY Expressed in various tissues including heart, pancreas, skeletal muscle, colon, spleen, liver, kidney, lung, peripheral blood and placenta.DOMAIN Contains 5 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. These motifs are not required for interaction with PPARG.SIMILARITY Belongs to the DNA2/NAM7 helicase family.CAUTION PubMed:12189208 experiments have been carried out partly in rat and partly in human.UniProtQ9BYK81EQUAL2649EQUALReactome Database ID Release 72442499Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=442499ReactomeR-HSA-4424991Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-442499.1SMARCD3SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3SMRD3_HUMANReactome DB_ID: 400141UniProt:Q6STE5 SMARCD3SMARCD3BAF60CFUNCTION Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Stimulates nuclear receptor mediated transcription. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity).SUBUNIT Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (Probable). Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3 (PubMed:18765789). Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (By similarity). May be a component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (PubMed:22952240, PubMed:26601204). Interacts with SMARCA4/BRG1/BAF190A (PubMed:14701856). Component of SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A (PubMed:29374058). The precise distribution of the related SMARCD1, SMARCD2 and SMARCD3 proteins among these and other SWI/SNF nucleosome-remodeling complexes is not fully known. May allow recruitment of SWI/SNF containing complexes specifically to promoters where these factors are located. Also interacts with several nuclear receptors including PPARG/NR1C3, RXRA/NR1F1, ESR1, NR5A1, NR5A2/LRH1 and other transcriptional activators including the HLH protein SREBF1/SREBP1 and the homeobox protein PBX1 (PubMed:14701856).TISSUE SPECIFICITY Isoform 2 and isoform 1 are expressed in brain, heart, kidney, placenta, prostate, salivary gland, spleen, testis, thyroid, trachea and uterus. Isoform 1 is also expressed in skeletal muscle and adipose tissue.SIMILARITY Belongs to the SMARCD family.UniProtQ6STE51EQUAL483EQUALReactome Database ID Release 72400141Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400141ReactomeR-HSA-4001411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-400141.1TGS1PIMTReactome DB_ID: 400176UniProt:Q96RS0 TGS1TGS1HCA137NCOA6IPPIMTFUNCTION Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation.SUBUNIT May form homooligomers. Interacts with CREBBP/CBP, EED/WAIT1, EP300/P300, NCOA6/PRIP, PPARBP/PBP and SMN.TISSUE SPECIFICITY Ubiquitously expressed. High expression in heart, skeletal muscle, kidney, liver and placenta.SIMILARITY Belongs to the methyltransferase superfamily. Trimethylguanosine synthase family.UniProtQ96RS01EQUAL853EQUALReactome Database ID Release 72400176Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400176ReactomeR-HSA-4001761Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-400176.1CHD9Chromodomain-helicase-DNA-binding protein 9CHD9_HUMANReactome DB_ID: 400163UniProt:Q3L8U1 CHD9CHD9KIAA0308KISH2PRIC320AD-013x0008FUNCTION Acts as a transcriptional coactivator for PPARA and possibly other nuclear receptors. Proposed to be a ATP-dependent chromatin remodeling protein. Has DNA-dependent ATPase activity and binds to A/T-rich DNA. Associates with A/T-rich regulatory regions in promoters of genes that participate in the differentiation of progenitors during osteogenesis (By similarity).SUBUNIT Interacts with PPARA. Probably interacts with ESR1 and NR1I3.TISSUE SPECIFICITY Widely expressed at low levels. In bone marrow, expression is restricted to osteoprogenitor cells adjacent to mature osteoblasts.PTM Phosphorylated on serine and tyrosine residues.SIMILARITY Belongs to the SNF2/RAD54 helicase family.UniProtQ3L8U11EQUAL2897EQUALReactome Database ID Release 72400163Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400163ReactomeR-HSA-4001631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-400163.1Reactome Database ID Release 72400216Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400216ReactomeR-HSA-4002161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-400216.11TBL1RTBL1XR1TBL1R_HUMANF-box-like/WD repeat-containing proteinReactome DB_ID: 351643UniProt:Q9BZK7 TBL1XR1TBL1XR1IRA1TBLR1FUNCTION F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of the N-Cor corepressor complex that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of N-Cor complex, thereby allowing cofactor exchange, and transcription activation.SUBUNIT Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1XR1, CORO2A and GPS2 (PubMed:11931768). Probable component of some E3 ubiquitin ligase complex. Interacts with histones H2B and H4 (PubMed:12628926). Interacts with MECP2; bridges interaction between MECP2 and NCOR1 (By similarity).TISSUE SPECIFICITY Widely expressed including the pituitary, hypothalamus, white and brown adipose tissue, muscle and liver.DOMAIN The F-box-like domain is related to the F-box domain, and apparently displays the same function as component of ubiquitin E3 ligase complexes.SIMILARITY Belongs to the WD repeat EBI family.UniProtQ9BZK71EQUAL514EQUALReactome Database ID Release 72351643Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351643ReactomeR-HSA-3516431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351643.11TBL1TBL1XTBL1X_HUMANReactome DB_ID: 351644UniProt:O60907 TBL1XTBL1XTBL1FUNCTION F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units (PubMed:14980219). Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of corepressor complexes that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of transcription repressor complexes, thereby allowing cofactor exchange (PubMed:21240272).SUBUNIT Homotetramer; dimer of dimers (PubMed:21240272). Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (PubMed:10809664, PubMed:21240272). Interacts with GPS2 (when sumoylated); leading to protect GPS2 against degradation by the proteasome (PubMed:24943844). Component of a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X (PubMed:11389839). Probably part of other corepressor complexes, that do not contain NCOR1 and NCOR2. Interacts with histones H2B, H3a and H4. Interacts with MECP2; recruits TBL1X to the heterochromatin foci (By similarity).TISSUE SPECIFICITY Ubiquitous.DOMAIN The F-box-like domain is related to the F-box domain, and apparently displays the same function as component of ubiquitin E3 ligase complexes.SIMILARITY Belongs to the WD repeat EBI family.UniProtO609071EQUAL577EQUALReactome Database ID Release 72351644Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351644ReactomeR-HSA-3516441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351644.11Activated PPARA:RXRAReactome DB_ID: 422412Peroxisome Proliferator Receptor Element (PPRE)Reactome DB_ID: 422139Reactome Database ID Release 72422139Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=422139ReactomeR-ALL-4221392Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-422139.21PPARA:fatty acid (Activated PPARA)Reactome DB_ID: 422413PPARAPeroxisome proliferator-activated receptor alphaPPAR-alphaReactome DB_ID: 400186UniProt:Q07869 PPARAPPARANR1C1PPARFUNCTION Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.SUBUNIT Heterodimer; with RXRA. This heterodimerization is required for DNA binding and transactivation activity. Interacts with NCOA3 coactivator. Interacts with CITED2; the interaction stimulates its transcriptional activity. Also interacts with PPARBP in vitro. Interacts with AKAP13, LPIN1, PRDM16 and coactivator NCOA6. Interacts with ASXL1 and ASXL2. Interacts with PER2. Interacts with SIRT1; the interaction seems to be modulated by NAD(+) levels (PubMed:24043310). Interacts with CRY1 and CRY2 (By similarity).TISSUE SPECIFICITY Skeletal muscle, liver, heart and kidney. Expressed in monocytes (PubMed:28167758).INDUCTION Down-regulated by aging.SIMILARITY Belongs to the nuclear hormone receptor family. NR1 subfamily.UniProtQ078691EQUAL468EQUALReactome Database ID Release 72400186Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400186ReactomeR-HSA-4001861Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-400186.11Converted from EntitySet in ReactomeLigands of PPARAReactome DB_ID: 400149ALAalpha-linolenic acidReactome DB_ID: 400174alpha-linolenic acid [ChEBI:27432]alpha-linolenic acidChEBICHEBI:27432Reactome Database ID Release 72400174Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400174ReactomeR-ALL-4001743Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-400174.3AAArachidonatearachidonic acidReactome DB_ID: 400137arachidonic acid [ChEBI:15843]arachidonic acidChEBICHEBI:15843Reactome Database ID Release 72400137Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400137ReactomeR-ALL-4001373Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-400137.3EPAeicosapentaenoic acidall-cis-5,8,11,14,17-icosapentaenoic acidReactome DB_ID: 400199all-cis-5,8,11,14,17-icosapentaenoic acid [ChEBI:28364]all-cis-5,8,11,14,17-icosapentaenoic acidChEBICHEBI:28364Reactome Database ID Release 72400199Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400199ReactomeR-ALL-4001993Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-400199.3LINAlinoleic acidReactome DB_ID: 400158linoleic acid [ChEBI:17351]linoleic acidChEBICHEBI:17351Reactome Database ID Release 72400158Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400158ReactomeR-ALL-4001584Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-400158.4Palmpalmitic acidhexadecanoic acidPalmitateReactome DB_ID: 400150hexadecanoic acid [ChEBI:15756]hexadecanoic acidChEBICHEBI:15756Reactome Database ID Release 72400150Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400150ReactomeR-ALL-4001503Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-400150.3Reactome Database ID Release 72400149Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400149ReactomeR-ALL-4001491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-400149.11Reactome Database ID Release 72422413Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=422413ReactomeR-HSA-4224131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-422413.11RXRARetinoic acid receptor RXR-alphaRXRA_HUMANReactome DB_ID: 381319UniProt:P19793 RXRARXRANR2B1FUNCTION Receptor for retinoic acid that acts as a transcription factor (PubMed:11162439, PubMed:11915042). Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:28167758, PubMed:17761950, PubMed:16107141, PubMed:18800767, PubMed:19167885). The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:17761950, PubMed:28167758). The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:1310260). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:20215566). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (PubMed:20215566, PubMed:9267036). Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (PubMed:10195690, PubMed:11915042, PubMed:28167758, PubMed:29021580). The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (PubMed:29021580). The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (PubMed:10195690). Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). Acts as an enhancer of RARA binding to RARE DNA element (PubMed:28167758). May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (PubMed:12145331, PubMed:15509776). Promotes myelin debris phagocytosis and remyelination by macrophages (PubMed:26463675). Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes (PubMed:25417649). Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (PubMed:30216632).SUBUNIT Homodimer (PubMed:10669605, PubMed:17761950). Heterodimer (via C-terminus) with RARA; required for ligand-dependent retinoic acid receptor transcriptional activity; association with RARA is enhanced by pulsatile shear stress (PubMed:28167758, PubMed:10698945, PubMed:15509776). Heterodimer with PPARA (via the leucine-like zipper in the LBD); the interaction is required for PPARA transcriptional activity (PubMed:10195690, PubMed:11915042, PubMed:11698662). Heterodimerizes with PPARG (PubMed:10882139, PubMed:11698662). Heterodimerizes (via NR LBD) with RARB (PubMed:29021580). Heterodimerizes with NR1H4; the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators (PubMed:30275017). Interacts with NCOA3 and NCOA6 coactivators (PubMed:9267036, PubMed:10567404). Interacts with coactivator FAM120B (By similarity). Interacts with coactivator PELP1, SENP6, SFPQ, DNTTIP2 and RNF8 (PubMed:16574651, PubMed:16912044, PubMed:11259580, PubMed:15047147, PubMed:14981089). Interacts with PRMT2 (PubMed:12039952). Interacts with ASXL1 (By similarity). Interacts with BHLHE40/DEC1, BHLHE41/DEC2, NCOR1 and NCOR2 (PubMed:19786558). Interacts in a ligand-dependent fashion with MED1 and NCOA1 (PubMed:19786558, PubMed:10882139, PubMed:11698662). Interacts with VDR (PubMed:28698609). Interacts with EP300; the interaction is decreased by 9-cis retinoic acid (PubMed:17761950). Heterodimer (via C-terminus) with NR4A1 (via DNA-binding domain); DNA-binding of the heterodimer is enhanced by 9-cis retinoic acid (PubMed:17761950, PubMed:15509776). NR4A1 competes with EP300 for interaction with RXRA and thereby attenuates EP300 mediated acetylation of RXRA (PubMed:17761950). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863).SUBUNIT (Microbial infection) Interacts (via the DNA binding domain) with HCV core protein; the interaction enhances the transcriptional activities of the RXRA/RARA and the RXRA/PPARA heterodimers.TISSUE SPECIFICITY Expressed in lung fibroblasts (at protein level) (PubMed:30216632). Expressed in monocytes (PubMed:26463675). Highly expressed in liver, also found in kidney and brain (PubMed:24275569, PubMed:2159111, PubMed:14702039).INDUCTION Down-regulated by aging (PubMed:26463675). Induced by pulsatile shear stress (PubMed:28167758).DOMAIN Composed of three domains: a modulating N-terminal domain (AF1 domain), a DNA-binding domain and a C-terminal ligand-binding domain (AF2 domain).PTM Acetylated by EP300; acetylation enhances DNA binding and transcriptional activity.PTM Phosphorylated on serine and threonine residues mainly in the N-terminal modulating domain (By similarity). Constitutively phosphorylated on Ser-21 in the presence or absence of ligand (By similarity). Under stress conditions, hyperphosphorylated by activated JNK on Ser-56, Ser-70, Thr-82 and Ser-260 (By similarity). Phosphorylated on Ser-27, in vitro, by PKA (PubMed:11162439). This phosphorylation is required for repression of cAMP-mediated transcriptional activity of RARA (PubMed:11162439).PTM Sumoylation negatively regulates transcriptional activity. Desumoylated specifically by SENP6.SIMILARITY Belongs to the nuclear hormone receptor family. NR2 subfamily.UniProtP197931EQUAL462EQUALReactome Database ID Release 72381319Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=381319ReactomeR-HSA-3813191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-381319.11Reactome Database ID Release 72422412Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=422412ReactomeR-HSA-4224121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-422412.11Reactome Database ID Release 72400154Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400154ReactomeR-HSA-4001541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-400154.1